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Lester, Rebecca 
ORCID: https://orcid.org/0000-0002-0259-9630
(2021)
Third-generation cephalosporin resistance in Blantyre, Malawi:
transmission and outcomes, Thesis (Doctoral), Liverpool School of Tropical Medicine.
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Abstract
Antimicrobial resistance occurs when microorganisms evolve to survive exposure to the antimicrobials previously successfully used to treat them. Ceftriaxone is a third-generation cephalosporin (3GC), which has long been the antibiotic of choice in many sub-Saharan African hospitals. Surveillance data from patients at Queen Elizabeth Central Hospital (QECH), in Blantyre, Malawi has shown a rapid proliferation of 3CG resistance (3GC-R) amongst key bloodstream isolates and the lack of availability of alternatives to ceftriaxone, means that these infections are frequently untreatable. Despite this, outcomes for patients with these infections in Malawi are unknown. I hypothesise that 3GC-R BSI is associated with poor outcomes for patients in Malawi, carrying a high mortality and morbidity for individual patients and a significant economic burden on the healthcare provider. Gut mucosal carriage of 3GCR-E generally precedes invasive infection and I further hypothesise that community household level determinants are driving a high prevalence of 3GC-R carriage amongst individuals living in urban Blantyre.
To address these hypotheses, I present the findings of two longitudinal cohort studies. The first, was a cohort of patients whose blood cultures were positive for Enterobacterales or Acinetobacter spp.. I use logistic regression and Cox proportional hazards models to determine the associations of 3GC-R on in-hospital mortality, hospital length of stay and survival. Healthcare resource use was obtained from review of the medical records and patients were interviewed to establish direct and indirect costs of admission as well as health-related quality of life (HRQoL) outcomes. I use multivariable models to estimate the effects of 3CG-R on these health economic outcomes. The second cohort was a community sample of randomly selected households in Blantyre. Stool samples were collected from adults and children from 110 households, over 6-months and processed for 3GC-R E. coli using selective Chromogenic agar. I first use hierarchical models to identify risk-factors for 3GC-R gut mucosal colonisation and then develop dynamical transmission models to explore transmission routes in more detail.
I find that patients with Enterobacterales and Acinetobacter spp. BSI have a high mortality and that there is a significant association between 3GC-R and death, as well as increased hospital length of stay. In addition, 3GC-R is associated with higher healthcare provider and patient level costs than sensitive infection as well as poorer HRQoL outcomes. The prevalence of 3GC-R E. coli colonisation in the community sample is high. Sampling during rainy season and higher prevalence within households are associated with 3CG-R carriage, suggesting that within household and environmental transmission are important. Dynamical modelling provides further insight into these transmission routes, suggesting that within household reservoirs and person-to-person transmission are important drivers of 3GC-R acquisition. Future iterations of the dynamical models I develop, should incorporate social network information and whole genome sequencing of cultured isolates, in order to identify where 3GC-R transmission pathways can be interrupted.
| Item Type: | Thesis (Doctoral) | ||||||||||||||
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| Subjects: | QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. QW Microbiology and Immunology > QW 50 Bacteria (General). Bacteriology. Archaea QY Clinical Pathology > QY 4 General works WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 260 Enterobacteriaceae and other enteric infections |
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| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department | ||||||||||||||
| Depositing User: | Lynn Roberts-Maloney | ||||||||||||||
| Date Deposited: | 12 Oct 2021 15:22 | ||||||||||||||
| Last Modified: | 12 Jan 2022 02:02 | ||||||||||||||
| URI: | https://archive.lstmed.ac.uk/id/eprint/19154 |
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